Using the consolidated Framework for Implementation Research to integrate innovation recipients' perspectives into the implementation of a digital version of the spinal cord injury health maintenance tool: a qualitative analysis.

BACKGROUND: Despite advances in managing secondary health complications after spinal cord injury (SCI), challenges remain in developing targeted community health strategies. In response, the SCI Health Maintenance Tool (SCI-HMT) was developed between 2018 and 2023 in NSW, Australia to support people with SCI and their general practitioners (GPs) to promote better community self-management. Successful implementation of innovations such as the SCI-HMT are determined by a range of contextual factors, including the perspectives of the innovation recipients for whom the innovation is intended to benefit, who are rarely included in the implementation process. During the digitizing of the booklet version of the SCI-HMT into a website and App, we used the Consolidated Framework for Implementation Research (CFIR) as a tool to guide collection and analysis of qualitative data from a range of innovation recipients to promote equity and to inform actionable findings designed to improve the implementation of the SCI-HMT. METHODS: Data from twenty-three innovation recipients in the development phase of the SCI-HMT were coded to the five CFIR domains to inform a semi-structured interview guide. This interview guide was used to prospectively explore the barriers and facilitators to planned implementation of the digital SCI-HMT with six health professionals and four people with SCI. A team including researchers and innovation recipients then interpreted these data to produce a reflective statement matched to each domain. Each reflective statement prefaced an actionable finding, defined as alterations that can be made to a program to improve its adoption into practice. RESULTS: Five reflective statements synthesizing all participant data and linked to an actionable finding to improve the implementation plan were created. Using the CFIR to guide our research emphasized how partnership is the key theme connecting all implementation facilitators, for example ensuring that the tone, scope, content and presentation of the SCI-HMT balanced the needs of innovation recipients alongside the provision of evidence-based clinical information. CONCLUSIONS: Understanding recipient perspectives is an essential contextual factor to consider when developing implementation strategies for healthcare innovations. The revised CFIR provided an effective, systematic method to understand, integrate and value recipient perspectives in the development of an implementation strategy for the SCI-HMT. TRIAL REGISTRATION: N/A.

Unmet healthcare needs, access to services and experiences with health providers among persons with spinal cord injury in Australia.

STUDY DESIGN: Cross-sectional survey. OBJECTIVES: Appropriate and timely lifelong access to healthcare following a spinal cord injury (SCI) is critical, yet unmet healthcare needs in this population are common. Poor experiences with healthcare providers can be a barrier to health-seeking behaviour, and we hypothesised that there would be an association between unmet healthcare needs and care experiences. This study aimed to: (1) describe healthcare provider utilisation in the past year, unmet care needs and satisfaction with healthcare services; (2) explore the association between experiences with healthcare providers and unmet healthcare needs; and (3) explore the association between healthcare provider utilisation and participant characteristics, including unmet healthcare needs. SETTING: Community. METHODS: Analysis of data for 1579 Australians aged ≥ 18, who were ≥ 1-year post-SCI and living in the community. Bayesian penalised regression was used to model six binary outcomes: unmet healthcare needs; the use of general practitioners (GPs), allied health practitioners, rehabilitation specialists; medical specialists; and hospitalisations in the past 12-months. RESULTS: Unmet needs were reported by 17% of participants, with service cost the common deterrent. There was evidence of an effect for provider experiences on unmet healthcare needs, but no evidence that unmet healthcare needs was associated with the use of GPs, allied health practitioners, and rehabilitation or medical specialists. CONCLUSIONS: Unmet healthcare needs were reported in the context of high healthcare use and large proportions of secondary conditions in a cohort with long-term SCI. Improved health access for people with SCI include better primary-secondary care collaboration is needed.

Unmet healthcare needs and health inequalities in people with spinal cord injury: a direct regression inequality decomposition.

BACKGROUND: Inequality in health is a prevalent and growing concern among countries where people with disabilities are disproportionately affected. Unmet healthcare needs explain a large part of the observed inequalities between and within countries; however, there are other causes, many non-modifiable, that also play a role. AIM: This article explores the difference in health across income levels in populations with spinal cord injury (SCI). SCI is of special interest in the study of health systems, as it is an irreversible, long-term health condition that combines a high level of impairment with subsequent comorbidities. METHODS: We estimated the importance of modifiable and non-modifiable factors that explain health inequalities through a direct regression approach. We used two health outcomes: years living with the injury and a comorbidity index. Data come from the International Spinal Cord Injury Survey (InSCI), which has individual data on people with SCI in 22 countries around the world. Due to the heterogeneity of the data, the results were estimated country by country. RESULTS: On average, the results exhibit a prevalence of pro-rich inequalities, i.e., better health outcomes are more likely observed among high-income groups. For the years living with the injury, the inequality is mostly explained by non-modifiable factors, like the age at the time of the injury. In contrast, for the comorbidity index, inequality is mostly explained by unmet healthcare needs and the cause of the injury, which are modifiable factors. CONCLUSIONS: A significant portion of health inequalities is explained by modifiable factors like unmet healthcare needs or the type of accident. This result is prevalent in low, middle, and high-income countries, with pervasive effects for vulnerable populations like people with SCI, who, at the same time are highly dependent on the health system. To reduce inequity, it is important not only to address problems from public health but from inequalities of opportunities, risks, and income in the population. HIGHLIGHTS: • Better health status is evident among high-income groups, which is reflected in pro-rich inequalities. • Age at the time of the injury is the most important factor to explain inequalities in years living with the injury. • Unmet health care needs are the most important factor to explain inequalities in comorbidities. • The inequality in health varies by country dependent upon socioeconomic factors.

Australian arm of the International Spinal Cord Injury (Aus-InSCI) Community Survey: 3. Drivers of quality of life in people with spinal cord injury.

STUDY DESIGN: Cross-sectional population-based survey for the Australian cohort of the International Spinal Cord Injury (InSCI) Community Survey. OBJECTIVES: To differentiate subgroups of people with spinal cord injury (SCI) who self-report good and poor overall quality of life (QoL) using domains of the International Classification of Functioning (ICF), and to evaluate how these factors contribute to QoL when considered together, while controlling confounders. SETTING: Australian survey data from four state-wide SCI services, one government insurance agency, and three not-for-profit consumer organisations. METHODS: Explanatory factors for QoL were compared between participants reporting poor vs. good QoL. Path models estimated total, direct and mediated contributions from each explanatory factor to QoL ratings after accounting for confounders. RESULTS: Most participants (62%) reported good or very good QoL, 12% reported poor or very poor QoL. When explanatory factors were considered together, the strongest total effects on QoL involved social integration (+0.36 SDs), subjective social position (+0.29), secondary health condition burden (-0.28), activity/participation problem burden (-0.26), day-to-day assistance (-0.26), mental health (+0.18), pain (-0.16), self-efficacy (+0.15), vitality (+0.14) and environmental barriers (-0.11). Effects of social integration, mental health, vitality, self-efficacy, pain and activity/participation problems were partly or wholly direct. CONCLUSION: Opportunities to improve QoL in people with SCI exist at every level of the health system. Virtually all aspects of the ICF framework make a substantive difference to QoL outcomes. Social and psychological factors and ability to complete desired activities have key direct effects and influence effects of secondary health condition burden and environmental barriers.

Australian arm of the International Spinal Cord Injury (Aus-InSCI) community survey: 1. population-based design, methodology and cohort profile.

STUDY DESIGN: Cross-sectional survey. OBJECTIVES: To describe design and methods of Australian arm of International Spinal Cord Injury (Aus-InSCI) community survey, reporting on participation rates, potential non-response bias and cohort characteristics. SETTING: Survey of community-dwelling people with SCI at least 12 months post-injury, recruited between March 2018 and January 2019, from state-wide SCI services, a government insurance agency and not-for-profit consumer organisations across four Australian states. METHODS: The Aus-InSCI survey combined data for people with SCI from nine custodians, using secure data-linkage processes, to create a population-based, anonymised dataset. The Aus-InSCI questionnaire comprised 193 questions. Eligibility, response status and participation rates were calculated. Descriptive statistics depict participant characteristics. Logistic regression models were developed for probability of participation, and inverse probability weights generated to assess potential non-response bias. RESULTS: 1579 adults with SCI were recruited, a cooperation rate of 29.4%. Participants were predominantly male (73%), with 50% married. Mean age was 57 years (range 19-94) and average time post-injury 17 years (range 1-73). Paraplegia (61%) and incomplete lesions (68%) were most common. Males were more likely than females to have traumatic injuries (p < 0.0001) and complete lesions (p = 0.0002), and younger age-groups were more likely to have traumatic injuries and tetraplegia (p < 0.0001). Potential non-response bias evaluated using selected outcomes was found to be negligible in the Aus-InSCI cohort. CONCLUSIONS: The Aus-InSCI survey made efforts to maximise coverage, avoid recruitment bias and address non-response bias. The distributed, linked and coded (re-identifiable at each custodian level) 'virtual quasi-registry' data model supports systematic cross-sectional and longitudinal research.

BAALC gene expression tells a serious patient outcome tale in NPM1-wild type/FLT3-ITD negative cytogenetically normal-acute myeloid leukemia in adults.

Acute myeloid leukemia with normal cytogenetics (CN-AML) is the largest group of AML patients which is associated with a variegated patient outcome. Multiple molecular markers have been used to risk-stratify these patients. Estimation of expression of BAALC gene (Brain and Acute Leukemia, Cytoplasmic) mRNA level is one of the predictive markers which has been identified in multiple studies. In this study, we examined the clinical and prognostic value of BAALC gene expression in 149 adult CN-AML patients. We also utilized multi-omics databases to ascertain the association of BAALC gene expression with comprehensive molecular and clinicopathologic features in AML. BAALC overexpression was associated with CD34 positivity on leukemic blasts (p = 0.0026) and the absence of NPM1 gene mutation (p < 0.0001), presence of RUNX1 gene mutation (p < 0.001) and poor patient outcomes, particularly in NPM1-wild type/FLT3-ITD negative adult CN-AML patients. Additionally, BAALC expression was associated with the alteration of methylation of its promoter. Further, pathway analysis revealed that BAALC expression is correlated with MYC targets and Ras signalling. We conclude that high BAALC expression associates with poor patient outcome in NPM1-wild type/FLT3-ITD negative adult CN-AML patients.

Prognostic utility of key copy number alterations in T cell acute lymphoblastic leukemia.

T-cell acute lymphoblastic leukemia (T-ALL) is a genetically heterogeneous disease, characterized by an abnormal transformation of T cells into highly proliferative leukemic lymphoblasts. Identification of common genetic alterations has provided promising opportunities for better risk stratification in T-ALL. Current treatment in T-ALL still poses the major challenge of integrating the knowledge of molecular alterations in the clinical setting. We utilized the Multiplex Ligation Dependent Probe Amplification (MLPA) method to determine the frequency of common copy number alterations (CNAs) in 128 newly diagnosed T-ALL patients. We also studied the association of these CNAs with patient's clinical characteristics and survival. The highest frequency of deletion was observed in CDKN2A (59.38%), followed by CDKN2B (46.88%), LMO1 (37.5%), and MTAP (28.12%). PTPN2 (22.66%), PHF6 (14.06%), and MYB (14.06%) had the highest number of duplication events. A total of 89.06% patients exhibited CNAs. STIL::TAL1, NUP214::ABL1, and LMO2::RAG2 fusions were observed in 5.47%, 3.12%, and 0.78% of patients, respectively. CDKN2A, CDKN2B, and PTPN2 gene deletions were mainly observed in pediatric patients, while CNAs of NF1 and SUZ12 were observed more frequently in adults. In pediatric patients, alterations in CDKN2B, CASP8AP2, and AHI1 were associated with poor prognosis, while SUZ12 and NF1 CNAs were associated with favorable prognosis. In adult patients, ABL1 CNA emerged as an independent indicator of poor prognosis. The observed molecular heterogeneity in T-ALL may provide the basis for variations observed in clinical response in T-ALL and MLPA based CNA detection may help in risk stratification of these patients.

Demographics of Cauda Equina Syndrome: A Population-Based Incidence Study.

INTRODUCTION: Cauda equina syndrome (CES) has significant medical, social, and legal consequences. Understanding the number of people presenting with CES and their demographic features is essential for planning healthcare services to ensure timely and appropriate management. We aimed to establish the incidence of CES in a single country and stratify incidence by age, gender, and socioeconomic status. As no consensus clinical definition of CES exists, we compared incidence using different diagnostic criteria. METHODS: All patients presenting with radiological compression of the cauda equina due to degenerative disc disease and clinical CES requiring emergency surgical decompression during a 1-year period were identified at all centres performing emergency spinal surgery across Scotland. Initial patient identification occurred during the emergency hospital admission, and case ascertainment was checked using ICD-10 diagnostic coding. Clinical information was reviewed, and incidence rates for all demographic and clinical groups were calculated. RESULTS: We identified 149 patients with CES in 1 year from a total population of 5.4 million, giving a crude incidence of 2.7 (95% CI: 2.3-3.2) per 100,000 per year. CES occurred more commonly in females and in the 30-49 years age range, with an incidence per year of 7.2 (95% CI: 4.7-10.6) per 100,000 females age 30-39. There was no association between CES and socioeconomic status. CES requiring catheterization had an incidence of 1.1 (95% CI: 0.8-1.5) per 100,000 adults per year. The use of ICD-10 codes alone to identify cases gave much higher incidence rates, but was inaccurate, with 55% (117/211) of patients with a new ICD-10 code for CES found not to have CES on clinical notes review. CONCLUSION: CES occurred more commonly in females and in those between 30 and 49 years and had no association with socioeconomic status. The incidence of CES in Scotland is at least four times higher than previous European estimates of 0.3-0.6 per 100,000 population per year. Incidence varies with clinical diagnostic criteria. To enable comparison of rates of CES across populations, we recommend using standardized clinical and radiological criteria and standardization for population structure.

Factors Related to Engagement in Employment After Spinal Cord Injury in Australia: A Cross-sectional Study.

OBJECTIVE: To explore the association between sociodemographic, health, functional independence, and environmental variables with engagement in paid work for people with spinal cord injury (SCI). DESIGN: Self-reported, cross-sectional Australian data from a large international SCI survey. SETTING: Community-based. PARTICIPANTS: 1189 working-age people with SCI (18-67 years) or aged >67 years and engaged in paid employment. Respondents were community based and at least 1 year after injury. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Employment and work integration variables. Bayesian penalized regression was used to determine associations between 23 predictor variables and engagement in paid work. RESULTS: Most participants (87%) were employed pre-injury, with 39% in paid employment at the time of the survey. Participants who attained a master's/doctoral degree (odds ratio [OR]=3.01; 95% credible interval [CrI], 1.63, 5.44) and those married (OR=1.68; 95% CrI, 1.13, 2.49) were more likely to be engaged in paid work. Women (OR=0.55; 95% CrI, 0.37, 0.81), people receiving a disability pension (OR=0.17; 95% CrI, 0.13, 0.24), and older participants (OR=0.75; 95% CrI, 0.63, 0.90) were less likely to be in paid work. Working participants identified hardships including problems completing their work (60%) and accessing the workplace (32%), as well as unmet needs relating to assistive devices required for completing their work (50%). CONCLUSIONS: Findings from the current study can assist in directing resources to subgroups within the SCI population who need greater assistance or intervention related to employment outcomes, including through vocational rehabilitation services/programs. Unmet needs and workplace issues expressed by employed individuals identify gaps in work integration and satisfaction that could affect employment sustainability that need to be addressed.

Australian arm of the International Spinal Cord Injury (Aus-InSCI) Community Survey: 2. Understanding the lived experience in people with spinal cord injury.

STUDY DESIGN: Cross-sectional survey. OBJECTIVES: To identify common problems across key domains of functioning, health and wellbeing, as well as evaluate self-reported quality of life (QoL) by people with SCI, examining differences by age, gender, injury characteristics and level of mobility. SETTING: Data from four state-wide SCI clinical services, one government insurance agency and three not-for-profit consumer organisations. METHODS: Participants were 18 years or over with SCI and at least 12 months post-injury, recruited between Mar'18 and Jan'19. The Aus-InSCI questionnaire comprised 193 questions, including socio-demographics, SCI characteristics, body functions and structures, activities and participation, environmental and personal factors, and appraisal of health and well-being. General linear model was used to examine differences in functioning and QoL. RESULTS: Participants (mean age 57 years, range 19-94 years) with tetraplegia and/or complete injuries had more health problems, activity/participation problems and environmental barriers. However, self-rated overall QoL did not differ for injury level or completeness. Participants with more recent injuries exhibited lower independence levels, more mental health problems and poorer satisfaction with self and their living conditions. Major activity/participation problems related to intimate relationships and accessing public transportation. Less than half of the working age population were engaged in paid work. The top two environmental barriers frequently related to accessing public places or homes and unfavourable climatic conditions. CONCLUSIONS: This large, comprehensive community survey draws a detailed picture of the lived experience of people with SCI in Australia, identifying priority needs, gaps in services and barriers to achieving a full and satisfying life.

Application and effect of hybrid grinding techniques on the quality of stone chakki atta (whole wheat flour) and flat bread.

Industrially packaged whole wheat flour (atta) is manufactured in motorized stone chakkis, which consumes more electric power. Present study is aimed towards evaluating the effect of hybrid grinding technique of wheat using roller mill on its grinding characteristics and quality of chakki atta and chapatti. Wheat was passed through the pair of first break rolls in MLU 202 with the roll gaps of 1 and 0.9 mm for two different samples. Electrical parameters for grinding energy were compared and the pre-milled wheat was ground in the stone chakki. Atta obtained from 2 different variations and control stone chakki atta were compared for physico-chemical, rheological and chapati making quality. Damaged starch increased from 15.25 for control atta to 17.3% for 0.9 mm sample, whereas, farinograph water absorption increased from 75.9 to 78.9% respectively. Chapatis were prepared and sensory studies were carried out. Chapati colour was found to be brighter for 0.9 mm sample.

Expression pattern, regulation, and clinical significance of TOX in breast cancer.

Thymocyte selection-associated high mobility group box protein (TOX) is a transcription factor implicated in the regulation of T cell exhaustion during chronic infection and cancer. While TOX is being targeted for cancer immunotherapy, limited information is available about its significance in breast cancer and other solid tumors. We performed a comprehensive analysis of TOX gene expression, its epigenetic regulation, protein localization, relation to tumor infiltrating immune cell composition, and prognostic significance in breast cancer using publicly available datasets. Our results suggest an inverse correlation between TOX expression and DNA methylation in tumor cells. However, its expression is elevated in tumor infiltrating immune cells (TIICs), which may compensates for the total TOX levels in the tumor as a whole. Furthermore, higher TOX levels in tumors are associated with T cell exhaustion signatures along with presence of active inflammatory response, including elevated levels of T cell effector cytokines. Survival analysis also confirmed that higher expression of TOX is associated with better prognosis in breast cancer. Therefore, expression of TOX may serve as a novel prognostic marker for this malignancy.

A neuro-cardiac self-regulation therapy to improve autonomic and neural function after SCI: a randomized controlled trial protocol.

BACKGROUND: Spinal cord injury (SCI) is associated with autonomic imbalance and significant secondary conditions, including cardiac and brain dysfunction that adversely impact health and wellbeing. This study will investigate the effectiveness (intention-to-treat) of a neuro-cardiac self-regulation therapy to improve autonomic and neural/brain activity in adults with SCI living in the community. METHODS: A two-arm parallel, randomised controlled trial in which adults with SCI living in the community post-rehabilitation will be randomly assigned to a treatment or control group. The treatment group (N = 60) aged 18-70 years with a chronic traumatic or non-traumatic SCI, will receive intervention sessions once per week for 10 weeks, designed to regulate autonomic activity using computer-based feedback of heart rate variability and controlled breathing (called HRV-F). Comprehensive neurophysiological and psychological assessment will occur at baseline, immediate post-treatment, and 6 and 12-months post-treatment. Primary outcome measures include electrocardiography/heart rate variability (to assess autonomic nervous system function) and transcranial doppler sonography (to assess cerebral blood circulation in basal cerebral arteries). Secondary outcomes measures include continuous blood pressure, electroencephalography, functional near-infrared spectroscopy, respiration/breath rate, electrooculography, cognitive capacity, psychological status, pain, fatigue, sleep and quality of life. Controls (N = 60) will receive usual community care, reading material and a brief telephone call once per week for 10 weeks and be similarly assessed over the same time period as the HRV-F group. Linear mixed model analysis with repeated measures will determine effectiveness of HRV-F and latent class mixture modelling used to determine trajectories for primary and selected secondary outcomes of interest. DISCUSSION: Treatments for improving autonomic function after SCI are limited. It is therefore important to establish whether a neuro-cardiac self-regulation therapy can result in improved autonomic functioning post-SCI, as well as whether HRV-F is associated with better outcomes for secondary conditions such as cardiovascular health, cognitive capacity and mental health. TRIAL REGISTRATION: The study has been prospectively registered with the Australian and New Zealand Clinical Trial Registry ( ACTRN12621000870853 .aspx). Date of Registration: 6th July 2021. Trial Sponsor: The University of Sydney, NSW 2006. Protocol version: 22/07/2021.

Employment outcomes following spinal cord injury: a population-based cross-sectional study in Australia.

STUDY DESIGN: Self-reported cross-sectional data for the Australian cohort participating in the International Spinal Cord Injury Community survey. OBJECTIVES: To contextualise post-injury employment for people with spinal cord injury (SCI) in Australia, including work participation rates, time to resuming work, underemployment and pre- and post-SCI employment changes. SETTING: Australian survey data from four state-wide SCI services, one government insurance agency and three not-for-profit consumer organisations across New South Wales, Queensland, South Australia and Victoria. METHODS: Data were analysed from 1579 participants with SCI who are at least 1-year post discharge from an inpatient facility. Survey measures included 16-items dedicated to employment. Pre- and post-injury job titles were based on the International Standard Classification of Occupations (ISCO-08) major classification. A mix of chi-squared, t-test and negative binomial regression were used to analyse data. RESULTS: The absolute post-injury employment rate was 49.9%, with one-third of the sample currently working. Pre-injury employment and engagement with vocational rehabilitation resulted in higher employment rates. Individuals who were unable to return immediately following inpatient rehabilitation took mean 28 months (SD, 35.9) to return. Time to employment was significantly lengthier for those without pre-injury jobs, at 59.7 months [SD, 43.8] (p < 0.001). Engagement in less manual roles increased post-injury, accounting for three quarters of post-SCI jobs. Underemployment was identified by 16.6% of those currently working. CONCLUSIONS: While there are current services and programmes in place in Australia that support post-injury employment, findings indicate a need for more comprehensive early intervention focused services targeted towards employers and individuals.

Twelve tips for integrating ultrasound guided peripheral intravenous access clinical skills teaching into undergraduate medical education.

Peripheral Intravenous access (PIV) is a procedure undertaken by Medical Practitioners and Non-Medical Practitioners. Traditional PIV uses a visual and tactile technique to locate blood vessels close to the surface of the skin. Chronic medical conditions, dehydration, obesity and recurrent intravenous access can make PIV challenging. Ultrasound (US) guided PIV is recommended to aid the identification of the arm arteries and veins and improve the success rate of needle placement in difficult cases. Medical and non-medical schools, and hospital organisations, are recognising the importance of US guided PIV education for undergraduate and postgraduate Medical and Non-Medical Practitioners. This to promote independence, efficiency and to improve patient safety. The aim of this 12 tips article is to highlight the considerations and practicalities of integrating and delivering, a practical based skills (PBS) session, on the use of US guided practice as an adjunct in difficult PIV, into the undergraduate medical education curricula.

A prospective cohort study investigating contributors to mild cognitive impairment in adults with spinal cord injury: study protocol.

BACKGROUND: Studies report rates of mild cognitive impairment (MCI) in spinal cord injury (SCI) range between 10 and 60%. This broad estimate of MCI in SCI is most likely a result of: (i) inconsistent operationalization of MCI; (ii) heterogeneity among individuals with SCI; (iii) failure to account for MCI subtypes, thereby adding to the heterogeneity of samples; and, (iv) poor control for traumatic brain injury (TBI) that obscures differentiation of MCI attributable to TBI versus other factors. There is a paucity of longitudinal studies following the course of MCI in SCI, and none that account for multiple predictors of MCI, including interactions among predictors. METHODS: An inception cohort longitudinal study will assess approximately 100 individuals aged 17-80 years with acute SCI, with measures taken at three timepoints (baseline, 3 months post-baseline, and 12 months post-injury). Data relevant to medical care received within the first 24-48 h of presentation to the emergency department will be analysed, as will measures of cognition, injury characteristics, medical history, personal factors, psychological status, psychosocial functioning, and quality of life. Latent class mixture modelling will determine trajectories for the primary outcome of interest, cognitive functioning and its subtypes, and secondary outcomes of interest such as depression. Multiple regression analyses will identify predictors of MCI and its subtypes. DISCUSSION: The prospective design will reveal change in cognitive functioning across time and unveil different outcome trajectories; thus addressing the lack of knowledge on trajectories of MCI and MCI subtypes in SCI. Through subtyping MCI, we hope to yield groups of cognitively impaired individuals with SCI that are potentially more homogenous and thereby stable and predictable. This is the first study to capture emergency department and acute care diagnostic evidence of mild TBI, which has been poorly controlled in previous studies. Our study will also be the first to distinguish the contribution of TBI from other factors to the development of MCI in individuals with SCI. TRIAL REGISTRATION: The study was prospectively registered with the Australian and New Zealand Clinical Trial Registry ( ACTRN12619001702101 ) on 3rd December 2019.

Electrical stimulation for treating pressure ulcers.

BACKGROUND: Pressure ulcers (also known as pressure sores, decubitus ulcers or bedsores) are localised injuries to the skin or underlying tissue, or both. Pressure ulcers are a disabling consequence of immobility. Electrical stimulation (ES) is widely used for the treatment of pressure ulcers. However, it is not clear whether ES is effective. OBJECTIVES: To determine the effects (benefits and harms) of electrical stimulation (ES) for treating pressure ulcers. SEARCH METHODS: In July 2019 we searched the Cochrane Wounds Specialised Register; the Cochrane Central Register of Controlled Trials (CENTRAL); Ovid MEDLINE (including In-Process & Other Non-Indexed Citations); Ovid Embase and EBSCO CINAHL Plus. We also searched clinical trials registries for ongoing and unpublished studies, and scanned reference lists of relevant included studies as well as reviews, meta-analyses and health technology reports to identify additional studies. We did not impose any restrictions with respect to language, date of publication or study setting. SELECTION CRITERIA: We included published and unpublished randomised controlled trials (RCTs) comparing ES (plus standard care) with sham/no ES (plus standard care) for treating pressure ulcers. DATA COLLECTION AND ANALYSIS: Two review authors independently selected trials for inclusion, extracted data, and assessed risk of bias. We assessed the certainty of evidence using GRADE. MAIN RESULTS: We included 20 studies with 913 participants. The mean age of participants ranged from 26 to 83 years; 50% were male. ES was administered for a median (interquartile range (IQR)) duration of five (4 to 8) hours per week. The chronicity of the pressure ulcers was variable, ranging from a mean of four days to more than 12 months. Most of the pressure ulcers were on the sacral and coccygeal region (30%), and most were stage III (45%). Half the studies were at risk of performance and detection bias, and 25% were at risk of attrition and selective reporting bias. Overall, the GRADE assessment of the certainty of evidence for outcomes was moderate to very low. Nineteen studies were conducted in four different settings, including rehabilitation and geriatric hospitals, medical centres, a residential care centre, and a community-based centre. ES probably increases the proportion of pressure ulcers healed compared with no ES (risk ratio (RR) 1.99, 95% confidence interval (CI) 1.39 to 2.85; I2 = 0%; 11 studies, 501 participants (512 pressure ulcers)). We downgraded the evidence to moderate certainty due to risk of bias. It is uncertain whether ES decreases pressure ulcer severity on a composite measure compared with no ES (mean difference (MD) -2.43, 95% CI -6.14 to 1.28; 1 study, 15 participants (15 pressure ulcers) and whether ES decreases the surface area of pressure ulcers when compared with no ES (12 studies; 494 participants (505 pressure ulcers)). Data for the surface area of pressure ulcers were not pooled because there was considerable statistical heterogeneity between studies (I2 = 96%) but the point estimates for the MD of each study ranged from -0.90 cm2 to 10.37 cm2. We downgraded the evidence to very low certainty due to risk of bias, inconsistency and imprecision. It is uncertain whether ES decreases the time to complete healing of pressure ulcers compared with no ES (hazard ratio (HR) 1.06, 95% CI 0.47 to 2.41; I2 = 0%; 2 studies, 55 participants (55 pressure ulcers)). We downgraded the evidence to very low certainty due to risk of bias, indirectness and imprecision. ES may be associated with an excess of, or difference in, adverse events (13 studies; 586 participants (602 pressure ulcers)). Data for adverse events were not pooled but the types of reported adverse events included skin redness, itchy skin, dizziness and delusions, deterioration of the pressure ulcer, limb amputation, and occasionally death. We downgraded the evidence to low certainty due to risk of selection and attrition bias and imprecision. ES probably increases the rate of pressure ulcer healing compared with no ES (MD 4.59% per week, 95% CI 3.49 to 5.69; I2 = 25%; 12 studies, 561 participants (613 pressure ulcers)). We downgraded the evidence to moderate certainty due to risk of bias. We did not find any studies that looked at quality of life, depression, or consumers' perception of treatment effectiveness. AUTHORS' CONCLUSIONS: ES probably increases the proportion of pressure ulcers healed and the rate of pressure ulcer healing (moderate certainty evidence), but its effect on time to complete healing is uncertain compared with no ES (very low certainty evidence). It is also uncertain whether ES decreases the surface area of pressure ulcers. The evidence to date is insufficient to support the widespread use of ES for pressure ulcers outside of research. Future research needs to focus on large-scale trials to determine the effect of ES on all key outcomes.

An exhaustive compilation on chemistry of triazolopyrimidine: A journey through decades.

The triazolopyrimidine scaffold represents one of the privileged structure in chemistry, and there has been an increase in number of studies utilizing this scaffold and its derivatives. Optimization of synthetic protocols such as aza-Wittig reaction, [3 + 2] cycloaddition reaction along with previous methods including condensation with 1,3-dicarbonyl substrates and oxidation of aminopyrimidine Schiff bases have been performed to obtain desired triazolopyrimidines. The triazolopyrimidine ring has been extensively used as a template in medicinal chemistry for its diverse pharmacological properties. Several medicinally active molecules possessing triazolopyrimidine scaffold, either fused or coupled with other heterocycles, have been reported in the literature, highlighting the significance of this nucleus. Interestingly, the unique triazolopyrimidine scaffold also exhibits an impressive potential as a ligand for the synthesis of several metal complexes with significant biological potential. Literature provides enough evidence of exhaustive exploration of this scaffold as a ligand for the chelates of platinum, ruthenium and other metals. This review aims to be a comprehensive and general summary of the different triazolopyrimidine syntheses, their use as ligands for the synthesis and development of metal complexes as medicinal agents and their main biological activities.

Evidence-based care in high- and low-risk groups following whiplash injury: a multi-centre inception cohort study.

BACKGROUND: Studies aimed at improving the provision of evidence-based care (EBC) for the management of acute whiplash injuries have been largely successful. However, whether EBC is broadly provided and whether delivery of EBC varies based on risk of non-recovery, is uncertain. Receiving EBC should improve recovery, though this relationship has yet to be established. Further, mitigating the effect of EBC is the relationship with the practitioner, a phenomenon poorly understood in WAD. This study aimed to determine the proportion of individuals with whiplash, at differing baseline risk levels, receiving EBC. This study also aimed to determine whether receiving EBC and the therapeutic relationship were associated with recovery at 3 months post injury. METHODS: Participants with acute whiplash were recruited from public hospital emergency departments, private physiotherapy practices, and State Insurance Regulatory Authority (SIRA) databases. Participants completed questionnaires at baseline (demographics, risk of non-recovery) and 3-months (treatment received, risk identification, therapeutic relationship) post injury. Primary health care providers (HCPs) treating these participants also completed questionnaires at 3-months. Recovery was defined as neck disability index ≤4/50 and global perceived effect of ≥4/5. RESULTS: Two-hundred and twenty-eight people with acute whiplash, and 53 primary care practitioners were recruited. The majority of the cohort reported receiving EBC, with correct application of the Canadian C-spine rule (74%), and provision of active treatments (e.g. 89% receiving advice) high. Non-recommended (passive) treatments were also received by a large proportion of the cohort (e.g. 50% receiving massage). The therapeutic relationship was associated with higher odds of recovery, which was potentially clinically significant (OR 1.34, 95% CI 1.18-1.62). EBC was not significantly associated with recovery. CONCLUSIONS: Guideline-based knowledge and practice has largely been retained from previous implementation strategies. However, recommendations for routine risk identification and tailored management, and reduction in the provision of passive treatment have not. The therapeutic relationship was identified as one of several important predictors of recovery, suggesting that clinicians must develop rapport and understanding with their patients to improve the likelihood of recovery.

Reversible host cell remodeling underpins deformability changes in malaria parasite sexual blood stages.

The sexual blood stage of the human malaria parasite Plasmodium falciparum undergoes remarkable biophysical changes as it prepares for transmission to mosquitoes. During maturation, midstage gametocytes show low deformability and sequester in the bone marrow and spleen cords, thus avoiding clearance during passage through splenic sinuses. Mature gametocytes exhibit increased deformability and reappear in the peripheral circulation, allowing uptake by mosquitoes. Here we define the reversible changes in erythrocyte membrane organization that underpin this biomechanical transformation. Atomic force microscopy reveals that the length of the spectrin cross-members and the size of the skeletal meshwork increase in developing gametocytes, then decrease in mature-stage gametocytes. These changes are accompanied by relocation of actin from the erythrocyte membrane to the Maurer's clefts. Fluorescence recovery after photobleaching reveals reversible changes in the level of coupling between the membrane skeleton and the plasma membrane. Treatment of midstage gametocytes with cytochalasin D decreases the vertical coupling and increases their filterability. A computationally efficient coarse-grained model of the erythrocyte membrane reveals that restructuring and constraining the spectrin meshwork can fully account for the observed changes in deformability.